Membrane-bound proteins and enzymes (for instance channels, receptors, and transporters) are involved in critical cellular processes, yet our understanding of these important biological molecules at molecular levels lags behind those of soluble proteins. For example, while thousands of X-ray crystal structures of soluble proteins are known, only about 30 structures of unique membrane proteins are currently available. A significant barrier to the structural characterization of membrane proteins is that membrane proteins are generally synthesized at low levels in cells. Obtaining significant quantities (even at milligrams scale) of purified membrane proteins for biochemical and biophysical studies has been a major obstacle.
Systems that can afford very high yields of recombinant soluble proteins are ineffective for membrane protein expression. For example, the three most popular and powerful commercially available recombinant protein expression vehicles, the bacteria Escherichia coli with T7 phage promoter-driven plasmids, the baculovirus Autograph californica nuclear polyhedrosis virus in Sporodoptera frugiperda cell lines, and the methylotrophic yeast Pichia pastoris with the alcohol oxidase promoter-driven plasmids, work well only for soluble proteins. Many expression systems fail to provide good production of membrane proteins because they lack a powerful promoter and/or a suitable cellular compartment to house the recombinant membrane proteins at significant levels.
A membrane protein production system would be indispensable and would allow scientists to tackle many currently intractable problems in membrane protein biochemistry.